Skin is the largest organ in the body of vertebrates, and composed of, from outside to inside, epidermis, dermis, and hypodermis. Keratinocytes in epidermis and fibroblasts in dermis are responsible for the body protection from mechanical or chemical damages and for wound healing. Wound healing, a complicated process, is a world-wide issue and costly for people of all ages. As proven by the Food and Drug Administration (FDA), there is merely one agent for would healing, all-trans retinoic acid. As described in literature, this agent is capable of promoting the expression of collagen and diminishing the amount of matrix metalloproteinase (MMP), and however, the side effects, such as skin stimulation or skin peeling, come along with the use of all-trans retinoic acid, which limits the applicability thereof. Steroid is another option for wound healing, but it makes collagen degraded and inhibits wound repair after being taken for a long period of time.
At the early stage of wound healing, fibroblasts around the wound migrate to start wound closure. With such a migration of the fibroblasts, the wound closure is initiated and newborn tissues resist the differentiation of the fibroblasts. See Wound Repair Regen 2009; 17: 88-98 and Am J Pathol 2001; 159: 1009-20. Such a phenomenon is characterized by the expression profiles of skin cells and growth factors, and the change of extracellular matrix (ECM). The proliferation and migration of the keratinocytes and fibroblasts benefit the progress of wound healing. Transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and platelet-derived growth factor-αβ (PDGF-αβ) have been proven as the main growth factors involved in the proliferation of skin cells. ECM is sited around the skin cells and within connective tissues for strengthening the cellular structure and mediating the cellular behavior. Collagen is abundant in ECM and the richest protein in connective tissues.
TGF-β is involved in cell differentiation, adhesion, proliferation, and migration, and ECM precipitation. During wound healing, TGF-β produced by keratinocytes, fibroblasts, macrophages, and platelets is significant for connective tissue regeneration, inflammation, and epidermis reformation. See J Invest Dermatol 2007; 127: 2656-67. Generally, it is recognized that TGF-α is able to mediate wound contract, cell migration, and scar formation. VEGF, also called vascular permeability factor, is secreted by keratinocytes, fibroblasts, macrophages, neutrophils, platelets, endothelial cells, and smooth muscle cells and is a mediating factor for endothelial cell migration, proliferation, and penetration during angiogenesis. PDGF-αβ plays a key role in the process of skin cell proliferation. As such, it is thought that these growth factors have effects on skin cell proliferation or wound healing.
MMP, comprising over 20 different zinc peptidases of the metzincin superfamily, is for the maintenance and turnover of macromolecules of ECM, such as collagen. MMP-1, also called interstitial collagenase, initiates the degradation of ECM and cooperates with other MMP to promote the degradation of collagen. Phorbol 12-myristate 13-acetate (PMA), known as an activator for protein kinase C, phosphorylates c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) to produce MMP-1, and inhibits tissue inhibitor of metalloproteinase-1 (TIMP-1). The reconstruction and synthesis of collagen in ECM are of importance for cell proliferation and wound healing.
Ginger is the rhizome of the plant Zingiber officinale, and has been widely used for food flavoring. As documented in Chinese medicine, ginger has been used as a treatment for allergy, asthma, constipation, diabetes, gingivitis, nervous diseases, rheumatism, stroke, toothache, and anti-microorganism infection. See Drug Metabol Drug Interact 2001; 18: 159-90, J Nat Prod 2009; 72: 950-3, Food Chem Toxicol 2007; 45: 683-90, and Phytother Res 2010a; 24: 1825-30. Moreover, literature has said that ginger has been used for treatment of chemotherapy-associated nausea, suppression of platelet aggregation, and inhibition of cyclooxygenase and nitric oxide synthase. See Thromb Res 2001; 103: 387-97, Wound Repair Regen 2009; 17: 99-107, Bioorg Chem 2001; 29: 156-63, and J Ethnopharmacol 1989; 26: 129-36. Other literature has repeatedly reported that ginger extract has positive biological functions on wound healing either in vivo or in vitro. See Wound Repair Regen 2009; 17: 306-6 and J Dermatol Sci 2001; Suppl 1: S68-S75.
As described above, research up to now shows that ginger has effects on the promotion of skin cell proliferation and migration. Therefore, an agent for wound healing is desirable and is needed to be provided and produced synthetically in the near future, if the active component for the promotion of skin cell proliferation and migration in ginger is discovered.